Advertisement

Journal of NeuroVirology

, Volume 7, Issue 2, pp 149–154 | Cite as

Infection and establishment of latency in the dog brain after direct inoculation of a nonpathogenic strain of herpes simplex virus-1

  • Sandra L. Springer
  • Charles H. Vite
  • Ara C. Polesky
  • Santosh Kesari
  • Nigel W. Fraser
  • John H. Wolfe
Short Communication

Abstract

A number of diseases affecting the CNS occur in the dog and can be used as models for gene therapy in a large brain. HSV-1 has several potential advantages as a vector to transfer genes into the CNS. However, the ability of HSV-1 to infect CNS cells varies among species and no information was available for the dog. When the nonpathogenic 1716 strain of HSV-1 was injected into the brains of normal dogs it established a latent infection without signs of pathology. Thus, it appears to be suitable as a vector for therapeutic, or marker genes, in this species.

Keywords

LAT gene therapy vector animal model 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Berthomme H, Lokensgard J, Yang L, Margolis T, Feldman LT (2000). Evidence for a bidirectional element located downstream from the herpes simplex virus type 1 latency-associated promoter that increases its activity during latency. J Virol 74: 3613–3622.CrossRefPubMedGoogle Scholar
  2. Card JP, Rinaman L, Lynn RB, Lee BH, Meade RP, Miselis RR, Enquist LW (1993). Pseudorabies virus infection of the rat central nervous system: ultrastructural characterization of viral replication, transport, and pathogenesis. J Neurosci 13: 2515–2539.PubMedGoogle Scholar
  3. Deatly AM, Spivack JG, Lavi E, Fraser NW (1987). RNA from an immediate early region of the HSV-1 genome is present in the trigeminal ganglia of latently infected mice. Proc Natl Acad Sci USA 84: 3204–3208.CrossRefPubMedGoogle Scholar
  4. Deshmane SL, Valyi-Nagy T, Block T, Maggioncalda J, Wolfe JH, Dillner A, Fraser NW (1995). An HSV-1 containing the rat β-glucuronidase cDNA inserted within the LAT gene is less efficient than the parental strain at establishing a transcriptionally active state during latency in neurons. Gene Ther 2: 209–217.PubMedGoogle Scholar
  5. Dobson AT, Margolis TP, Sedarati F, Stevens JG, Feldman LT (1990). A latent, nonpathogenic HSV-1-derived vector stably expresses beta-galactosidase in mouse neurons. Neuron 5: 353–360.CrossRefPubMedGoogle Scholar
  6. Fraser NW, Spivack JG, Wroblewska Z, Block T, Deshmane SL, Valyi-Nagy T, Natarajan R, Gesser R (1991). A review of the molecular mechanism of HSV-1 latency. Curr Eye Res 10 (Suppl): 1–14.CrossRefPubMedGoogle Scholar
  7. Glorioso JC, Goins WF, Schmidt MC, Oligino T, Krisky DM, Marconi PC, Cavalcoli JD, Ramakrishnan R, Poliani PL, Fink DJ (1997). Engineering herpes simplex virus vectors for human gene therapy. Adv Pharmacol 40: 103–136.CrossRefPubMedGoogle Scholar
  8. Goins WF, Sternberg LR, Croen KD, Krause PR, Hendricks RL, Fink DJ, Straus SE, Levine M, Glorioso JC (1994). A novel latency-active promoter is contained within the herpes simplex virus type 1 UL flanking repeats. J Virol 68: 2239–2252.PubMedGoogle Scholar
  9. Haskins M, Abkowitz J, Aguirre G, Casal M, Evans S, Hasson C, Just C, Lexa F, Miranda S, Schuchman E, Simonaro C, Thrall M, Wang P, Weil M, Weimelt S, Wolfe J, Patterson D (1997). Bone marrow transplantation in animal models of lysosomal storage diseases. In: Correction of genetic diseases by transplantation IV. Ringden O, Hobbs JR, Stewart CG (eds). London: COGENT Press, pp 1–11.Google Scholar
  10. Ho DY, Mocarski ES (1989). Herpes simplex virus latent RNA (LAT) is not required for latent infection in the mouse. Proc Natl Acad Sci USA 86: 7596–7600.CrossRefPubMedGoogle Scholar
  11. Huang QS, Valyi-Nagy T, Kesari S, Fraser NW (1997). β-Gal enzyme activity driven by the HSV LAT promoter does not correspond to β-gal RNA levels in mouse trigeminal ganglia. Gene Ther 4: 797–807.CrossRefPubMedGoogle Scholar
  12. Kesari S, Randazzo BP, Valyi-Nagy T, Huang QS, Brown SM, MacLean AR, Lee VM-Y, Trojanowski JQ, Fraser NW (1995). Therapy of experimental human brain tumors using a neuroattenuated herpes simplex virus mutant. Lab Invest 73: 636–648.PubMedGoogle Scholar
  13. MacLean AR, Ul-Fareed M, Robertson L, Harland J, Brown SM (1991). Herpes simplex virus type 1 deletion variants 1714 and 1716 pinpoint neurovirulence-related sequences in Glasgow strain 17+ between immediate early gene 1 and the ‘a’ sequence. J Gen Virol 72: 631–639.CrossRefPubMedGoogle Scholar
  14. Markert J, Medlock M, Rabkin S, Gillespie G, Todo T, Hunter W, Palmer C, Feigenbaum F, Tornatore C, Tufaro F, Martuza R (2000). Conditionally replicating herpes simplex virus mutant, G207, for the treatment of malignant glioma: results of a phase I trial. Gene Ther 7: 867–874.CrossRefPubMedGoogle Scholar
  15. Martuza RL, Malick A, Markert JM, Ruffner KI, Coen DM (1991). Experimental therapy of human glioma by means of a genetically engineered virus mutant. Science 252: 854–856.CrossRefPubMedGoogle Scholar
  16. Ostrander EA, Galibert F, Patterson DF (2000). Canine genetics comes of age. Trend Genet 16: 117–124.CrossRefGoogle Scholar
  17. Patterson DF, Haskins ME, Jezyk PF, Giger U, Meyers-Wallen VN, Aguirre G, Fyfe JC, Wolfe JH (1988). Research on genetic diseases: Reciprocal benefits to animals and man. J Am Vet Med Assoc 193: 1131–1144.PubMedGoogle Scholar
  18. Rampling R, Cruickshank G, Papanastassiou V, Nicoll J, Hadley D, Brennan D, Petty R, MacLean A, Harland J, McKie E, Mabbs R, Brown M (2000). Toxicity evaluation of replication-competent herpes simplex virus (ICP 34.5 null mutant 1716) in patients with recurrent malignant glioma. Gene Ther 7: 859–866.CrossRefPubMedGoogle Scholar
  19. Randazzo BP, Kesari S, Gesser RM, Alsop D, Ford JC, Brown SM, MacLean AR, Fraser NW (1995). Treatmentof experimental intracranial murine melanoma with a neuroattenuated herpes simplex virus-1 mutant. Virology 211: 94–101.CrossRefPubMedGoogle Scholar
  20. Roizman B, Sears AE (1995). Herpes simplex viruses and their replication. In Virology, 3rd ed. Fields BN, Knipe DM, Howley PM (eds). New York: Raven Press, pp 2231–2296.Google Scholar
  21. Stevens JG, Wagner EK, Devi-Rao GB, Cook ML, Feldman LT (1987). RNA complementary to a herpes virus gene mRNA is prominent in latently infected neurons. Science 235: 1056–1059.CrossRefPubMedGoogle Scholar
  22. Stroop WG, Rock DL, Fraser NW (1984). Localization of herpes simplex virus in the trigeminal and olfactory systems of the mouse central nervous system during acute and latent infections by in situ hybridization. Lab Invest 51: 27–38.PubMedGoogle Scholar
  23. Summers BA, Cummings JF, deLahunta A (1995). Veterinary neuropathology. St Louis: Mosby-Year Book, pp 307–401.Google Scholar
  24. Wolfe JH, Deshmane SL, Fraser NW (1992). Herpesvirus vector gene transfer and expression of β-glucuronidase in the central nervous system of MPS VII Mice. Nat Genet 1: 379–384.CrossRefPubMedGoogle Scholar
  25. Wolfe JH, Martin CE, Deshmane SL, Reilly JJ, Kesari SK, Fraser NW (1996). Increased susceptibility to the pathogenic effects of wild-type and recombinant herpesviruses in MPS VII mice compared to normal siblings. J NeuroVirol 2: 417–422.CrossRefPubMedGoogle Scholar
  26. Zhu J, Kang W, Wolfe JH, Fraser NW (2000). Significantly increased expression of β-glucuronidase in the central nervous system of mucopolysaccharidosis type VII mice from the latency-associated transcript promoter in a nonpathogenic herpes simplex virus type 1 vector. Mol Ther 2: 82–94.CrossRefPubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2001

Authors and Affiliations

  • Sandra L. Springer
    • 1
  • Charles H. Vite
    • 1
  • Ara C. Polesky
    • 1
  • Santosh Kesari
    • 2
  • Nigel W. Fraser
    • 1
    • 2
  • John H. Wolfe
    • 1
    • 2
  1. 1.Department of Pathobiology, Center for Comparative Medical Genetics, School of Veterinary MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.The Wistar InstitutePhiladelphiaUSA

Personalised recommendations